NM_006312.6:c.7296G>A

Variant names:

• chr12-124326258-C-T
• rs187350105
• NM_006312.6:c.7296G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6 BP7 BS2

The NM_006312.6(NCOR2):​c.7296G>A​(p.Ser2432Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000766 in 1,559,662 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0038 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00044 (3 hom.)
• Consequence: NCOR2 NM_006312.6 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -3.77
• Publications: 1 publications found

Genes affected

NCOR2 (HGNC:7673): (nuclear receptor corepressor 2) This gene encodes a nuclear receptor co-repressor that mediates transcriptional silencing of certain target genes. The encoded protein is a member of a family of thyroid hormone- and retinoic acid receptor-associated co-repressors. This protein acts as part of a multisubunit complex which includes histone deacetylases to modify chromatin structure that prevents basal transcriptional activity of target genes. Aberrant expression of this gene is associated with certain cancers. Alternate splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Apr 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 12-124326258-C-T is Benign according to our data. Variant chr12-124326258-C-T is described in ClinVar as Benign. ClinVar VariationId is 3050430.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-3.77 with no splicing effect.
• BS2: High AC in GnomAd4 at 574 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006312.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOR2	NM_006312.6	MANE Select	c.7296G>A	p.Ser2432Ser	synonymous	Exon 48 of 49	NP_006303.4	Q9Y618-1
	NCOR2	NM_001206654.2		c.7266G>A	p.Ser2422Ser	synonymous	Exon 47 of 48	NP_001193583.1	C9J0Q5
	NCOR2	NM_001077261.4		c.7128G>A	p.Ser2376Ser	synonymous	Exon 47 of 48	NP_001070729.2	C9JE98

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCOR2	ENST00000405201.6	TSL:1 MANE Select	c.7296G>A	p.Ser2432Ser	synonymous	Exon 48 of 49	ENSP00000384018.1	Q9Y618-1
	NCOR2	ENST00000429285.6	TSL:1	c.7266G>A	p.Ser2422Ser	synonymous	Exon 46 of 47	ENSP00000400281.2	C9J0Q5
	NCOR2	ENST00000404621.5	TSL:1	c.7128G>A	p.Ser2376Ser	synonymous	Exon 46 of 47	ENSP00000384202.1	C9JE98

Frequencies

GnomAD3 genomes AF: 0.00377 AC: 574 AN: 152222 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0131

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000788 AC: 133 AN: 168866 AF XY: 0.000601

Gnomad AFR exome AF: 0.0112

Gnomad AMR exome AF: 0.000741

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000141

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000441 AC: 620 AN: 1407322 Hom.: 3 Cov.: 31 AF XY: 0.000389 AC XY: 271 AN XY: 696430

African (AFR) AF: 0.0132 AC: 419 AN: 31722

American (AMR) AF: 0.000788 AC: 29 AN: 36806

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24764

East Asian (EAS) AF: 0.00 AC: 0 AN: 36532

South Asian (SAS) AF: 0.0000124 AC: 1 AN: 80434

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46940

Middle Eastern (MID) AF: 0.000534 AC: 3 AN: 5618

European-Non Finnish (NFE) AF: 0.000109 AC: 118 AN: 1086130

Other (OTH) AF: 0.000857 AC: 50 AN: 58376

GnomAD4 genome AF: 0.00377 AC: 574 AN: 152340 Hom.: 0 Cov.: 33 AF XY: 0.00348 AC XY: 259 AN XY: 74496

African (AFR) AF: 0.0131 AC: 543 AN: 41578

American (AMR) AF: 0.00118 AC: 18 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68030

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.00173 Hom.: 2

Bravo AF: 0.00411

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	NCOR2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	8.1
DANN	Benign	0.92
PhyloP100		-3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs187350105; hg19: chr12-124810804;